Novel drug delivery technology

ABSTRACT

The invention relates to a novel drug delivery technology. More particularly the invention relates to a method of delivering at least one therapeutic compound or a formulation comprising the at least one therapeutic compound to a patient; to a throwaway or reusable device for delivering at least one therapeutic compound or a formulation comprising the at least one therapeutic compound to a patient in a manner as set out by the method; to a pioneer projectile for use in said method; to formulations for use in said method and to an injectate comprising a pioneer projectile and formulation. It also relates to a disposable component containing either a pioneer projectile or an injectate. The invention also relates to a throwaway or reusable device for delivering at least one therapeutic compound, or a formulation comprising the at least one therapeutic compound (hereafter drug) to a patient, and a method for administering a drug to a patient using said device. It also relates to a packaged drug for use with said device.

FIELD OF THE INVENTION

[0001] The present invention relates to a novel drug deliverytechnology. More particularly the invention relates to a method ofdelivering at least one therapeutic compound or a formulation comprisingthe at least one therapeutic compound to a patient; to a throwaway orreusable device for delivering at least one therapeutic compound or aformulation comprising the at least one therapeutic compound to apatient in a manner as set out by the method; to a pioneer projectilefor use in said method; to formulations for use in said method and to aninjectate comprising a pioneer projectile and formulation. It alsorelates to a disposable component containing either a pioneer projectileor an injectate. The present invention also relates to a throwaway orreusable device for delivering at least one therapeutic compound, or aformulation comprising the at least one therapeutic compound (hereafterdrug) to a patient, and a method for administering a drug to a patientusing said device. It also relates to a packaged drug for use with saiddevice.

BACKGROUND TO THE INVENTION

[0002] One route of administration for therapeutic compounds is throughthe skin. The skin is also one of the more efficient routes for deliveryof a therapeutic compound when compared to other standard deliveryroutes such as oral or pulmonary delivery.

[0003] Administration to the skin is most commonly undertaken using aneedle and syringe as a delivery system with the therapeutic compound ina liquid form.

[0004] Such a system has a number of associated problems including thepain and fear associated with needles, the fact they are really bestsuited to injecting liquids which are not necessarily the best way ofdelivering compounds to a patient and the fact that sharps are leftwhich create a disposal problem.

[0005] Drug delivery systems that do not incorporate needles are alsoused for injecting liquids through the skin and this is achieved by thedelivery system creating a very fine, high velocity liquid jet thatcreates its own hole through the skin. There are however a number ofproblems with such a method including splash back.

[0006] With both these forms of liquid delivery relatively large volumesof liquid are injected which, because they are incompressible, have totear the tissue apart in order to be accommodated.

[0007] However, drug injection through the skin does not have to beachieved with the drug in a standard liquid form. Solid form drugs havebeen successfully administered with the PowderJect system, which uses acompressed gas source to accelerate powdered drugs to a velocity atwhich they can penetrate the outer layers of the skin. This systemtypically employs powdered drug particles of less than 100 microns indiameter, which require a velocity of several hundred metres per secondin order to penetrate human tissue. However the system has its owninherent problems such as controlled delivery.

[0008] It has also been shown in the past that solid rods or splintersof a therapeutic compound can be pushed, at a relatively low velocity,into the skin without the requirement for a needle although moretraditionally these are delivered as implants.

[0009] The current transdermal drug delivery techniques can thus becategorised into groups based on the drug form and the velocity of theinjection as set out in table 1 below: TABLE 1 Drug Form Drug InjectionVelocity Liquid Solid High Velocity Liquid Jet Injector PowderJectSystems Drug darts Low Velocity Needle and Syringe Drug ‘Splinters’

[0010] Drug darts are disclosed in a number of publications. WO 96/40351(American Cyanamid) discloses an implant dart with a head of a solidplastics material which takes the form of a blade and a tubular bodythat contains one or more sustained release drug delivery implantpackages. Flexible stabilizing wings are provided on either side of thedart head which serve as a lock or barb to prevent the dart being pulledout after entry. The dart has on outside diameter of about 7 mm and alength of about 45 mm and is delivered with an injection gun which firesthe dart into an animal, but not a human, when a trigger is released.The propulsion mechanism delivers a force sufficient to impart a highaccelerating velocity of from 40-60 mph on the dart. To inject the dartat low speed it is necessary to make a small incision in the animal andoperate the push bar manually.

[0011] U.S. Pat. Nos. 3,948,263 and 4,326,524 also disclose ballisticdelivery devices. U.S. Pat. No. 3,948,263 discloses a ballistic implantwhich is fired from a .25 calibre rifle. The projectile exits at about900 ft/sec and can travel 20-40 ft before implanting into muscle some1-2 inches beneath the skin. U.S. Pat. No. 4,326,524 discloses a soliddose ballistic projectile formed entirely of a cohesive mixturecomprising biologically active material, in the form of grindable solidparticles and a binder which is capable of withstanding the stressesimparted on impact. The projectile has a body portion with a diameter offrom 4.5 to 7.6 mm, with a conical nose portion with a base diametersmaller than the diameter of the body such that a slight shoulder regionis formed between the body and the nose. The end remote from the nose ispreferably concave to aid flight.

[0012] GB 2365100 is another example of a remote ballistic deliverydevice which is fired and attains velocities of greater than 500 m/s. Incontrast to those described above the device is slowed on impact so thatit does not enter the body but instead the device's nose is moved backsuch that a needle enters the body, and a drug is injected. Such adevice is not needleless.

[0013] CA1019638 discloses a projectile which is launched by aconventional air gun or bow. It comprises a head piece and a shaft, thehead piece pierces the animals flesh and the shaft breaks away. In oneembodiment the head piece is made of a porous material which retains aliquid drug through capillary action through launch and impact and whichreleases it by diffusion when it is inserted into the animal. In asecond embodiment the head piece takes the form of a hardened cake. Toaid penetration a metal or plastics tip may be provided. The drugdelivering element remaining in the skin is about 3 mm diameter by 13 mmin length.

[0014] U.S. Pat. No. 3,901,158 Ferb discloses a hypodermic projectilewhich is again fired from a rifle or pistol. It comprises a shatterablefront end of plastic or glass which breaks on impact releasing theliquid contents.

[0015] None of the described high velocity devices bear any resemblanceto the present invention in which the at least one therapeutic compoundor a formulation comprising the at least one therapeutic compound ispushed at low velocity from a device which contacts the skin and inwhich the pioneer projectile is water soluble, lipid soluble orotherwise biodegradable in the human or animal and is furthermoresignificantly smaller having a width or diameter of less than 3 mm inwidth, more preferably still less than 2.5 mm through 2 mm and 1.5 mm toabout 1 mm in width; a height of less than 10 mm in height, morepreferably about 1.5 to 2 mm in height and an aspect ratio of less than1:8, preferably less than 1:6, more preferably less than 1:4, morepreferably still less than 1:3, and most preferably about 1:1.5.

[0016] High velocity liquid systems are exemplified by U.S. Pat. No.116,313 Mc Gregor. Liquid is first ejected from a small orifice in aprobe at a very high velocity and pressure which will penetrate the skinand then the main charge of liquid is ejected at a lower velocity intothe channel formed by the initial penetration.

[0017] EP0139286 (Sumitomo Chemical Co Limited) disclosessustained-release preparations in the form of needle like or bar likeshapes, which comprise an active ingredient and a pharmaceuticallyacceptable biodegradable carrier. The sustained-release preparation canbe administered to the body by injection by pushing it through a hollowneedle or by implantation.

[0018] WO 94/22423 (Bukh Meditec A/S) discloses a drug administrationsystem. The method of parenteral administration comprises administeringa drug substance by penetrating the skin or the mucosa of a human or ananimal by a body with an appropriately formed solid pharmaceuticalcomposition. The body of the pharmaceutical composition may be needleshaped so as to avoid external penetration equipment. The solidpharmaceutical composition comprises at least one drug substance and hasa shape and/or strength to enable penetration. The composition is madeby mixing a material, preferably a polymer and optionally a filler withan active drug substance; extruding the mixture to form an elongatebody; drying it and forming a pointed end.

[0019] U.S. Pat. Nos. 5,542,920, 6,117,443 and 6,120,786 (Cherif Cheikh)all disclose needle-less parenteral introduction devices. A medicamentis made in the form of a solid needle having a pointed end that hassufficient structural integrity to penetrate the skin. The needles areless than 2 mm, preferably 0.2 to 0.8 mm, in diameter and 10 to 30 mm inlength.

[0020] U.S. Pat. No. 6,102,896 (Roser) is primarily directed to adisposable injector device for injecting controlled release watersoluble glass needles. It however also recognises that these glassneedles, which are about 1 mm in diameter by 10 mm in length and containa medicament may also be used as pioneer projectiles to produce a lowresistance pathway through the tissue along which a liquid suspension(exemplified as a drug in a suspension of PFC fluid) can flow. Thisdocument appears the first and only document to recognise that adissolvable pioneer projectile may be used to enable the introduction ofa medicament. It however fails to recognise that it may be used as ageneral technique for introducing medicaments in other forms. Indeedthis is readily apparent from the document in which a dry powderedformulation is made into a non viscous liquid by suspending it in PFC.

SUMMARY OF THE INVENTION

[0021] The present invention takes the concept of using a pioneerprojection (as disclosed in U.S. Pat. No. 6,102,896) further and followsfrom the applicants recognition that a pioneer projectile can be used asa means for introducing medicaments in forms other than a free flowing,non viscous liquid.

[0022] According to a first aspect of the present invention there isprovided a method of delivering at least one therapeutic compound or aformulation containing the at least one therapeutic compound to a humanor animal in the form of a needleless injection comprising:

[0023] i) Penetrating the skin with a water soluble, lipid soluble orotherwise biodegradable pioneer projectile having a diameter of lessthan 3 mm which is left in the human or animal; and

[0024] ii) Introducing directly, or substantially directly, behind thepioneer projectile, the at least one therapeutic compound or theformulation containing the at least one therapeutic compound, which atleast one therapeutic compound or the formulation containing the atleast one therapeutic compound is provided and delivered in a containedstate.

[0025] By contained state is meant either:

[0026] i) As a liquid contained by a membrane;

[0027] ii) As a liquid with a viscosity of at least 5000 centipoises(the viscosity of honey), more particularly at least 50,000 (theconsistency of mayonnaise) and most preferably still at least 100,000(the consistency of peanut butter), such that the liquid hascharacteristics more akin to a solid than a liquid i.e. they have adefinite shape as well as volume (and are not readily free flowing);

[0028] iii) As a semi-solid (having a viscosity and rigidityintermediate that of a solid or a liquid);

[0029] iv) As a paste (having a soft malleable consistency);

[0030] v) As a gel (a liquid dispersed in a solid) which materials canall be considered to have a degree of stiffness; or

[0031] vi) As a solid (a state in which the matter retains its ownshape).

[0032] Introducing a medicament in such a contained state has advantagesin that splash back and seepage can be avoided and more controlleddosages delivered when compared to a following non viscous liquidformulation. The viscous, semi solid or solid nature of the medicamentensures that the pioneer projectile is pushed to the requisite depth andis followed by the medicament rather than seeping around the sides ofthe projectile. The semi solid formulations, gels, pastes and solids arealso generally more stable than liquid formulations and are more patientcompliable.

[0033] Furthermore it will be appreciated that by introducing themedicament in a form other than as a non viscous liquid behind a pioneerprojectile it is possible to tailor the characteristics of themedicament for optimum pharmacokinetic delivery rather than forpenetration.

[0034] Similarly the pioneer projectile can be developed to haveoptimised penetrating capabilities independent of the medicament.

[0035] Preferably the pioneer projectile is independent of the at leastone therapeutic compound or the formulation containing the at least onetherapeutic compound.

[0036] Alternatively the pioneer projectile is independent of yet formsan integral part of the at least one therapeutic compound or theformulation containing the at least one therapeutic compound.

[0037] Most preferably the pioneer projectile forms a head to the atleast one therapeutic compound or the formulation containing the atleast one therapeutic compound.

[0038] The at least one therapeutic compound or the formulationcontaining the at least one therapeutic compound can take a number offorms.

[0039] In one embodiment the at least one therapeutic compound or theformulation containing the at least one therapeutic compound is a liquidcontained in a water soluble, lipid soluble or otherwise biodegradablemembrane.

[0040] In another embodiment the at least one therapeutic compound orthe formulation containing the at least one therapeutic compound isprovided in a solid form such as, for example, crystals, particles,granules, beads, rods, discs or a combination thereof.

[0041] In yet another embodiment the at least one therapeutic compoundor the formulation containing the at least one therapeutic compound isprovided as a viscous liquid, semi solid, gel or paste which may befurther supported, if desirable, by a water soluble lipid soluble orotherwise biodegradable membrane.

[0042] In the method of the invention the skin is penetrated and thetherapeutic compound administered at a low velocity. By low velocity ismeant less than 100 m/s. Preferably the velocity is less than 10 m/s,more preferably still less than 5 m/s and most preferably in the orderof a few m/s.

[0043] Since the injectate is pushed at a low velocity rather than firedat a high velocity it is possible to ensure that the dosage is alwaysdelivered to the correct (and same) depth under the skin. This meansthat the system can be used on different skin types and skin locationsand the dosage will still be delivered to the same depth.

[0044] According to a second aspect of the invention there is provided amethod of facilitating the delivery of at least one therapeutic compoundor a formulation containing the at least one therapeutic compound to ahuman or animal as a needleless injection comprising:

[0045] i) Providing a water soluble, lipid soluble or otherwisebiodegradable pioneer projectile having a diameter of less than 3 mmcapable of penetrating the human or animals skin; and

[0046] ii) Providing directly, or substantially directly, behind thepioneer projectile, the at least one therapeutic compound or theformulation containing the at least one therapeutic compound in acontained state.

[0047] The act of pushing the at least one therapeutic compound in thecontained state causes the pioneer projectile to penetrate the human oranimals skin and the therapeutic compound or the formulation containingthe at least one therapeutic compound follows the pioneer projectile andis introduced into the human or animal in the contained state.

[0048] The invention also extends to novel pioneer projectiles.

[0049] According to a third aspect of the present invention there isprovided a water soluble, lipid soluble or otherwise biodegradablepioneer projectile having a diameter of less than 3 mm, and which iscapable of penetrating the skin of a human or animal to therebyfacilitate the injection of at least one following therapeutic compoundor therapeutic compound containing formulation in a contained state,comprising:

[0050] i) A first “penetrating” face which in use penetrates the humanor animals skin; and

[0051] ii) Remote from the first face a second “driven” face which inthe course of injection is the face upon which a driving force isexerted through the contained therapeutic compound or therapeuticcompound containing formulation; characterised in that said pioneerprojectile has an aspect ratio (width to height) of less than 1:10.

[0052] Because the pioneer projectile has been developed separately ofthe medication it has been possible to reduce its size from one of atleast 10 mm in length to about a few millimetres. It has also beenpossible to optimise its shape such that it functions as a leading heador tip for a following contained formulation, the two components formingan injectate.

[0053] Preferably the pioneer projectile has an aspect ratio of lessthan 1:8, preferably less than 1:6, more preferably less than 1:4, morepreferably still less than 1:3, and most preferably about 1:1.5.

[0054] Preferably the pioneer projectile is less than 3 mm in width,more preferably still less than 2.5 mm, through 2 mm and 1.5 mm, toabout 1 mm in width.

[0055] Preferably the pioneer is less than 10 mm in height, morepreferably about 1.5 to 2 mm in height. By reducing the height to aminimum it is possible to maximise the amount of therapeutic compoundbeing injected. In this regard it should be noted that if the combinedpioneer projectile and following drug formulation is too long it mightnot be possible to deliver the drug to the optimum depth.

[0056] In one embodiment the pioneer projectile is free of anytherapeutic compound. In another embodiment it comprises at least onetherapeutic compound. Thus, for example it might be beneficial toinclude, for example, an antibiotic in the pioneer projectile or have itrelease a therapeutic compound at a different rate to the formulationin, for example, the case of insulin injections.

[0057] The skin penetrating face of the pioneer projectile preferablycomprises a cutting element to facilitate entry. This may take the formof a sharp point or an oblique edge. Alternatively the skin penetratingface may be blunt or gently curved.

[0058] In one embodiment the face for contacting the therapeuticcompound or therapeutic compound containing formulation in a containedstate is flat. Alternatively it may be concave or otherwise hollowed tofacilitate pushing and formulation containment.

[0059] The pioneer projectile may be made of any suitable material.Suitable materials are those hard and rigid enough to facilitatepenetration at low velocities. Preferred materials include glassymaterials e.g. the sugar glasses as noted in WO 98/41188 which materialsare included herein by reference. The term “sugar” thus covers not onlydisaccharide sugars, such as, trehalose, but also monosaccharide sugarsand their non reducing derivatives, such as, sugar alcohols including:mannitol, inositol, xylitol, ribitol and the like, which form a generalclass of stabilising glass-forming sugars and sugar derivatives. Theterm “sugar glass” is to be understood as covering not only glasseswhich are readily and rapidly dissolved in an aqueous environment, suchas, trehalose but also sugar glasses in which the sugar molecule hasbeen modified by the attachment of one or more hydrophobic side chainsto make the glass more slowly soluble in bodily fluids than the nativesugar in order to give controlled release characteristics.

[0060] In some circumstances the pioneer projectile may comprise abarrier material over at least the face that contacts the therapeuticcompound in a contained state or vice versa such that the respectivecomponents will not react with one another.

[0061] The invention also extends to novel formulations.

[0062] According to a fourth aspect of the present invention there isprovided a therapeutic compound or therapeutic compound containingformulation which is held in a contained state and adapted forintroduction into a human or animal in the form of a needlelessinjection behind a water soluble, lipid soluble or otherwisebiodegradable pioneer projectile having a diameter of less than 3 mm.

[0063] Preferably the formulation comprises less than 50 mg oftherapeutic compound in a volume of less than 50 mm³, more preferablyless than 10 mg of therapeutic compound in a volume of less than 10 mm³.

[0064] The therapeutic compound or therapeutic compound containingformulation may be provided as a liquid contained in water soluble,lipid soluble or otherwise biodegradable membrane.

[0065] In an alternative embodiment the therapeutic compound ortherapeutic compound containing formulation is provided in a solid formcomprising for example crystals, particles, granules, beads, rods, discsor a combination thereof which are generally likely to be more stablethan traditional non-viscous liquid formulations with a viscositysimilar to that of water e.g. 1 Centipoise or glucose e.g. 500Centipoises.

[0066] In a preferred embodiment the therapeutic compound or therapeuticcompound containing formulation is provided as a semi solid, gel orpaste. In this form it is particularly patient compliant and thetherapeutic compound is generally likely to be more stable than if itwere in a traditional non-viscous liquid formulation.

[0067] Where the therapeutic compound or therapeutic compound containingformulation is a viscous liquid, it preferably has a viscosity of atleast 10,000 Centipoises more preferably at least 50,000 Centipoises andmore preferably still at least 100,000 Centipoises.

[0068] The formulation may comprise an end piece beyond the therapeuticcompound or therapeutic compound which is free of the “active” beinginjected thus ensuring that the entire therapeutic compound enters thepatient in a unit dose rather than risk under or over dosing.

[0069] The therapeutic compound or therapeutic compound containingformulation may comprise a plurality of differently formulated elements.

[0070] The therapeutic compound or therapeutic compound containingformulation may be packaged in a cap, cartridge, carousel or cassette.

[0071] The invention also extends to an injectate comprising a pioneerprojectile and a therapeutic compound or therapeutic compound containingformulation.

[0072] According to a fifth aspect of the present invention there isprovided a needleless injectate for injection comprising:

[0073] a) A water soluble, lipid soluble or otherwise biodegradablepioneer projectile having a diameter of less than 3 mm; and

[0074] b) A therapeutic compound or therapeutic compound containingformulation which is held in a contained state behind the pioneerprojectile.

[0075] These components are as previously described.

[0076] The pioneer projectile and therapeutic compound or therapeuticcompound containing formulation may both be water soluble, lipid solubleor otherwise biodegradable to differing degrees.

[0077] A barrier may be provided between the pioneer projectile and thetherapeutic compound or therapeutic compound containing formulation.

[0078] The injectate may be contained/packaged in a cap, cartridge,carousel or cassette optionally together with a means, e.g. an ejectorpin, for pushing the injectate out of its container.

[0079] Alternatively the pioneer projectile and the therapeutic compoundor therapeutic compound containing formulation are contained/packaged inseparate caps, cartridges, carousels or cassettes.

[0080] The invention also extends to a device for injecting a pioneerprojectile and a therapeutic compound or therapeutic compound containingformulation.

[0081] According to a sixth aspect of the present invention there isprovided a needleless device (60) for injecting a water soluble, lipidsoluble or otherwise biodegradable pioneer projectile (10) having adiameter of less than 3 mm and at least one contained therapeuticcompound or therapeutic compound containing formulation (42) into ahuman or animal body, said device comprises a housing (62) containing amechanism (92) capable of generating a force which will cause a striker(84) to travel along a striker guide (86), said housing having an endface (100) which is in operative communication with a component (72)comprising a casing (74) having an aperture (76) in which is mounted anejector pin (78) and, therebelow, an injectate (40) comprising a pioneerprojectile (10) and a formulation (42) such that in use the striker willcontact the ejector pin and the injectate will be pushed out of thecasing as a single unit into the human or animal body.

[0082] The reference numerals given above are non-limiting but have beenincluded solely for the purpose of assisting the reader.

[0083] The term ejector pin is intented to cover a pin, piston, rod orlike member which functions to push the injectate from the aperture.

[0084] The power source for initiating or assisting the pushing may be amechanical spring in the form of, for example, a coiled spring or alever spring. Alternatively, a gas spring might be used or even anelectrically powered system. A mechanical spring would allow reuse ofthe delivery system although this would mean the user has to rechargethe spring between administrations. Alternatively, the spring(mechanical or gas) could be precharged during manufacture so that itcan only be used once and then the whole system would be thrown away. Ina reusable device there will be a throw away component containing thepioneer projectile or the pioneer projectile and the therapeuticcompound or therapeutic compound containing formulation.

[0085] The device preferably incorporates a safety mechanism to avoidaccidental actuation. Actuation might be triggered with a push button onthe device but preferably would be undertaken by pushing the deviceagainst the skin thus ensuring good contact with the skin on actuation.

[0086] In a reusable device the reusable component and the throw awaycomponent comprise means by which they are connected to one another.

[0087] The device may be adapted to inject multiple doses eithersequentially or simultaneously. In one embodiment the device comprises acartridge, carousel or cassette containing a plurality of pioneerprojectiles or a plurality of injectates comprising a pioneer projectileand a therapeutic compound or therapeutic compound containingformulation.

[0088] In another embodiment the device comprises a cap containing asingle pioneer projectile and a single unit dose of the therapeuticcompound or therapeutic compound containing formulation.

[0089] The various aspects described above give rise to a system havinga number of advantages over the prior art delivery methods and some ofthese are noted in table 2 below: TABLE 2 Benefit Justification 1 Canuse Many drugs are more stable in solid form formulations with than in aliquid state. A viscous liquid Increased Product formulation would bemore akin to a solid Stability. drug in terms of its stabilitycharacteristics because of the excipients that can be used 2 ImprovedProduct The increased stability with some com- Storage pounds may allowstorage of the final deliv- ery system at room temperature rather thanrequiring refrigeration 3 Reduced Risk Of Without the need for needlesthere is a re- Cross Infection duced risk of blood borne diseases 4Small Device Size Spring, trigger, injectate and piston are the maincomponents required 5 Cheap Device A spring is a cheap power source.Small overall number of device components 6 Reusable Device The designcan allow for the spring to be primed for reuse. Disposable componentswould be small in terms of size and cost but would include the componentholding the injectate or pioneer projectile 7 Variable Power Aspring-powered device could allow System the tension on the spring to bealtered for different skin types and skin positions on the body, ifnecessary. 8 Small Skin Response As experienced with splinters 9 QuietDevice Actuation of a spring powered delivery sys- tem will be quiet 10Easy to Understand Easy to comprehend the forces involved in DeliverySystem pushing a foreign body into the skin to a known depth. Easy tomeasure the physical characteristics required for a ‘dose’ of in-jectate of this size 11 Variable Dose With a viscous injectate it willbe possible to alter the dose injected 12 Self Injection With a simplesystem patients can inject themselves, thus reducing healthcare costs 13Controlled Depth Of Pushing the injectate into the skin rather thanPenetration Of The firing it enables a consistent and controlledDelivered Dose depth of penetration in the skin 14 Large Doses Largedoses of one or more drugs are achiev- Achievable able by having one ormore doses of injectate administered in the same injection

[0090] The concept behind the invention allows for a simple needlelessdrug delivery device that pushes a drug in a “contained” state.

[0091] A semi solid, paste or gel is the preferred form since unlike anon-viscous liquid it would follow the pioneer projectile. (Anon-viscous liquid can “splash back” and more easily seep around thetrack formed by the pioneer projectile.) Its stiffness relative to anon-viscous liquid also means it is easier to push than a non-viscousliquid material. The more solid in nature the better this is. Howeverfrom a comfort perspective a semi solid or paste or gel is more likelyto be patient compliant and dissolve more readily in the body.

[0092] The delivery device for delivering such an injectate (pioneerprojectile and formulation) could take a number of forms and severalsuch devices are described by way of example.

[0093] A first device described is a spring-powered device with thespring, triggering the pushing of a pin. The pin then engages theinjectate to push it into the skin with the pin being stopped by eitheran end stop within the device or by coming into contact with the skin,preferably over a relatively wide area (compared to the injectate) toreduce the force felt on the skin.

[0094] If the device is to be reusable then the component holding theinjectate might be detached from the rest of the device and thrown awayand a new disposable component attached before the next injection. Theinjection itself would occur in a matter of milliseconds after actuationand would seem instantaneous as far as the user is concerned.Alternatively the formulation might be injected from, for example, atube and a new pioneer projectile would be required for a furtherinjection.

[0095] By way of a further development the needleless device describedwith reference to the sixth aspect of the invention was furtherdeveloped with the aim of producing a simple, cheap drug delivery devicewhich is adaptable and able to deliver a drug in the form of not only aneedleless injectate but also other forms, such as, for example liquidformulations, and solid drug needles.

[0096] This aim is achieved by the provision of a device which isadapted to receive a packaged drug which is slidably mounted in thedevice such that in use the device is able to push the drug from itspackaging, the packaged drug being packaged such that the drug, whateverit's form, can be pushed from its packaging by the device.

[0097] It is another and independent aim to package different drug formsfor use with such a device.

[0098] This aim is achieved by the provision of a packaging adapted tobe attached to the device and which comprises a channel housing thedrug, and a drive pin or like element for pushing it out when actuatedby the device.

[0099] There are many possible product applications for such a deliverydevice and they include therapeutic, prophylactic and diagnosticapplications. Applications may be limited to those drugs that areadministered in relatively low doses because of the dose limitations foreach injection imposed by pushing. However, although each dose may belimited to less than 10 mg or a volume of less than 10 mm³ it would bepossible to administer more than one dose either concurrently orsequentially, if larger doses are required.

[0100] New laws in many states in the USA are declaring that safetyneedles must be used for injections whenever possible. These are needlesthat withdraw into a sheath as the needle is withdrawn from the patientso that the needle tip is not left exposed. This is to avoid the use ofa conventional needle which can result in accidental needle stickinjuries. A delivery system that either does not require a needle (orthat incorporates a needle that retracts) would be beneficial for the USmarket as well as other parts of the world that will, no doubt, followthe lead of the Americans.

[0101] Particular applications where the technology might be very wellsuited include:

[0102] Vaccines:—Vaccinations are one of the common reasons for peopleto need an injection and many people would rather risk catching adisease than have to be injected with a standard needle and syringe.Children in particular can often have a needle phobia Therefore a systemthat either does not incorporate a needle (or the needle is never seenby the patient) might help compliance with vaccines. In third worldcountries there is a great need for delivery systems for vaccines thatdo not involve needles. An added advantage of the new delivery system isthat using a non liquid dose therapeutic compound should assiststability of the active compounds and therefore the cold chain storagerequirements for the vaccine may be avoided.

[0103] Acute Emergencies:—The device is very quick and easy to use andtherefore well suited for self administration as well as administrationby an untrained assistant. There are a number of drugs, such as glucagon(hypoglycaemia), migraine treatments or adrenalin (anaphylactic shock)that are required when the patient may not be in a suitable condition toundertake the injection themselves. Glucagon and some of the migrainetreatments are normally supplied as a powder that have to be made upwith the diluent before the injection which means that they are notsuitable for administration by an untrained assistant. In addition, thepatient may, or may not be in a fit state to make up the drug let aloneadminister it. The present device would enable these and similar drugsto be administered in solid dosage form.

[0104] Diabetes:—Millions of people worldwide have to inject insulineither daily or several times a day. Most have to use a needle andsyringe although new delivery systems such as inhalers and insulin pumpsare becoming more popular. The advantage of the new delivery system isthat several different types of insulin can be administered in a soliddose form at one time. This can be done by having two or more shortpieces of different insulin formulations in e.g. a drug cassette. Thiscould allow a short as well as a long acting insulin to be injected atthe same time and thus reduce the requirement for multiple injectionsthroughout the day.

[0105] Although the applications above have been highlighted, thetechnology is suitable for administering many drugs that are required atthe dosage levels capable of being delivered by the system.

[0106] According to a seventh aspect of the present invention there isprovided a drug delivery device (210) comprising:

[0107] i) a housing (212);

[0108] ii) a means (214) for generating a force capable of pushing adrug (216) from a packaging (218) into a human or animal body;

[0109] iii) a means (220) for transmitting said force to push the drug(216) from the packaging (218) into the human or animal body; and

[0110] iv) a means (238, 242 b) for triggering the device.

[0111] The numbers are again included for illustrative purposes and arenot to be construed as limiting.

[0112] Such a device can be a reusable device which further comprises ameans (222) for receiving a packaged drug (2100); and a means (224) forpriming the device.

[0113] Alternatively the device can be a single use device in which casethe packaged drug (2100) will be an integral part of the device. Such adevice can be provided in a pre primed form which just needs triggeringor in a form requiring it to be primed.

[0114] A device according to the invention has a number of advantagescompared to current needle free devices.

[0115] It comprises a small number of components and is therefore cheapto manufacture and assemble. It is also relatively small (currently thesame size as a dry marker pen).

[0116] In a preferred embodiment of the device, it can only be actuatedby inserting a packaged drug and pushing the skin tensioning end of thepackaged drug against a solid object. The priming and actuation of thedevice by pushing the end of the device against the skin ensures thatthere is a reliable and consistent contact and tensioning of the skin ondelivery of the drug. Additionally, by setting the device such that theforce required to actuate it is from, for example, 20-30 Newton theforce will be too high for a patient to accidentally actuate the devicewithout pushing it firmly against the body's tensioned skin, therebyproviding a significant safety feature.

[0117] A spring and cap arrangement makes it is possible to adjust theactuation force by altering the tension on the spring. By screwing thecap further onto the upper barrel the spring is tensioned and byunscrewing it the force can be reduced. Alternatively, instead of a coilspring as the main power source, the device could incorporate any othertype of mechanical spring or a gas spring. In an alternative embodimentthe spring could be pre-tensioned during manufacture to avoid having totension the spring during the drug administration. This would result ina single use device in which case the packaged drug would most likely bean integral part of the device.

[0118] The velocity of the impact hammer during administration of thetherapeutic agent is less than 20 m/s, more preferably less than 10 m/s,more preferably still less than 5 m/s and most preferably in the orderof 0.1-2 m/s. The skilled man will appreciate that the actual speed mayvary with the mass of the impact hammer and thus the impact imparted onthe delivery dose. As a consequence the therapeutic agent is deliveredby a pushing action from the end of the packaged drug rather than by afiring action (as would be the case with a bullet leaving the barrel ofa gun).

[0119] To ensure that the device actuates automatically when the correctforce is applied the hammer has a shaped shoulder region which engages acorrespondingly shaped surface in a wall separating the upper and lowerbarrels. The device will actuate only when the substantiallyfrustoconical sections filly engage. This will be at the same mainspring tension every administration and if the administration is abortedbefore the frustoconical sections engage then the packaged drug can beremoved safely without leaving the device primed.

[0120] In a preferred embodiment the device can't be primed until thepackaged drug is attached thereto since it is the packaged drug thatacts against the piston in the device to cause the spring to betensioned. This makes the device particularly safe. It also means itcan't be actuated when not loaded such that an operator can't use thedevice in a belief they are providing an injection.

[0121] In the case of a reusable device a slewing spring returns theimpact hammer into it's non axially aligned position at the end of eachadministration.

[0122] Furthermore, because the reusable components of the system (allcomponents except those of the packaged drug) do not come into contactwith the target tissue for the drug administration they do need to besterile.

[0123] All components apart from the springs can be moulded making thedevice cheap to manufacture and the limited number of parts and theirease of assembly keeps assembling costs to a minimum.

[0124] A range of custom packaged drugs will fit the delivery device butpatients will not be able to easily introduce their own therapeuticcompounds into the drug cassettes (as can be done with a needle andsyringe).

[0125] The device is suitable for both human and veterinaryapplications.

[0126] The device is particularly suitable for self administration ofdrugs and requires minimal training.

[0127] According to an eighth and related aspect of the invention thereis provided a packaged drug (2100), for use with a drug delivery device,comprising a packaging (218) containing a drug (216), said packaging(218) comprising a housing (218 a, 218 b) having a channel (2106)running there through and in which is disposed a drive pin or otherelement (2108), a skin piercing means (2110; 2112), and the drug (216),said housing (218 a, 218 b) comprising

[0128] i) a region (2102) allowing the packaged drug (2100) to beslidably mounted to the drug delivery device (210); and

[0129] ii) an end (2104) adapted to engage and tension the skin.

[0130] In the case of a drug splinter the skin piercing means and thedrug may be one of the same.

[0131] Preferably the drug is disposed between the drive pin and theskin piercing means.

[0132] Preferably the packaged drug takes the form of a disposable endcap, cartridge, cassette or carousel, containing a single or multipledoses of the drug.

[0133] Preferably the region for engaging the packaged drug to the drugdelivery device in a slidable manner additionally comprises a means forpositively locking it to the device such that it can still slide withinthe device but will not fall out under gravity. Such a means might be asprung pin or spigot which exerts a frictional force against the deviceor a mechanism whereby the packaged drug is inserted in a particularorientation and turned so that it is precluded from being removed unlessit is turned back into the position in which it was allowed to enter.

[0134] In a first embodiment the packaged drug houses either a pioneerprojectile in combination with a drug in a contained state, morepreferably a solid, or a drug splinter (a single solid entity).

[0135] In a second embodiment the piercing means comprises a needle withtwo sharp ends, one for puncturing the skin and the other for puncturinga membrane of a receptacle containing the drug, the drug being releasedinto the needle from where it drains out into the body through theneedle. The drug is preferably a liquid and is contained in thereceptacle which is disposed in the channel. Advantageous features ofthe device include a spacer between the membrane piercing end of theneedle and the membrane of the drug containing receptacle to prevent theneedle coming into contact with the membrane prior to actuation. Thespacer is either resilient or compressible and may be supported by aplate attached to the needle. The receptacle is preferably sealed by thedrive pin or other like element.

[0136] In a third embodiment the packaged drug may contain a drug in anystate (e.g. solid, semi solid or liquid), the actuation of the devicecausing, in a two step operation, first the entry of a pioneerprojectile and only then the release of the drug from a thin walledtube. Release of the drug may optionally require the breaking of amembrane supporting the drug in the tube.

[0137] In a variation of this embodiment the pioneer projectile, whichis located immediately in front of the thin tube, could be replaced by aretractable needle tip which is, or is integral with, the thin walledtube. As per embodiment 1 and 2 described above, the thin walled tubecould have a compression spring or other resilient member associatedtherewith to withdraw the thin walled tube following the injection.

[0138] A particularly clever feature of this embodiment is the form ofthe drive pin or element which has a plurality of flexible or frangiblearms, in the embodiment illustrated two, extending from its main body.These arms extend outwards (splay) when they ride over a ramped surfaceprovided on the housing, are forced away from the body, and ride over alip on the tube as a consequence of the flex or frangibility. Inconsequence the body of the drive pin or element can move down the tube.This arrangement facilitates a two step operation whereby in a firststep the drive pin or element acts on the tube causing it to move andpush the pioneer projectile into the skin, and then, and only when thefirst step is complete, the arms are caused to splay and/or snap therebyallowing the drive pin body to push the drug contents from the tube. Inthe case where the arms are frangible the arms will snap off as a resultof an area of weakness formed about the shoulder region and fall into acavity about the ramped region. A frangible system has two advantages:firstly it should ensure full injection occurs, and secondly it willmean the packaged drug can't be re-used. The ramp is preferably“circular” in design, taking the form of a frustoconical surface. Thishas the advantage that it can be easily moulded and does not require thearms to be orientated for contact.

[0139] Depending on the diameter of the thin walled tube and theviscosity of the therapeutic compound, the thin walled tube may need tobe sealed, or partially sealed to avoid premature loss of the drug.However the action of the drive pin body will be sufficient to break anyseal allowing the drug to be released and pushed into the patient.

[0140] An advantage of the packaged drugs exemplified is their smallcheap sub-assembly. They are also easy to handle and place into thedevice prior to administration. Their size also facilitates easy storagein, for example, refrigerators.

[0141] The packaged drug may be sealed in a foil pouch or the like toprevent ingress of, for example, moisture, oxygen, light, bacteria orother drug degrading or contaminating agents.

[0142] In those embodiments having a pioneer projectile the tip will, inmost instances, be positioned a few millimetres from the end of the drugcassette so that it is moving when it strikes the target tissue.

[0143] Preferably the end adapted to engage and tension the skincomprises one or more projections about the channel exit, mostpreferably in the form of an annular ring, as such an arrangement mosteffectively tensions the skin.

[0144] A retention system may advantageously be employed to hold thedrug and pioneer projectile in place in the channel. This might beachieved by, for example, extruding or moulding the drug and/or pioneerprojectile with a number of small splines or other features along theirouter surface. These splines or other features would provide africtional fit but would not prohibit the drug from being administered.Alternatively, the channel of the packaging might have a small feature,such as, for example, a retaining bump or other projection over whichthe pioneer projectile and drug have to be pushed.

[0145] A tamper or use evident seal or other indicator means mayadditionally be placed over the top end of the packaged drug so thatwhen e.g. the seal is broken it is obvious that the packaged drug hasnot been interfered with and/or is spent.

[0146] Additionally or alternatively a seal may be place over the exitof the channel of the packaged drug. It would be preferable to removethis seal prior to administration of the drug but it would best bedesigned such that the administration could be carried out through theseal just in case it wasn't removed by the user.

[0147] According to yet a further aspect of the invention there isprovided a method of delivering a drug to a human or animal using adevice and/or packaged drug according to the invention.

[0148] The various aspects of the invention will now he described, byway of example only, with reference to the following Figures andExamples.

BRIEF DESCRIPTION OF THE DRAWINGS

[0149]FIGS. 1a-e are embodiments of pioneer projectiles of varyingshapes and sizes;

[0150]FIGS. 2a-c are embodiments of pioneer projectiles with hollowdriven faces;

[0151]FIGS. 3a-d are embodiments of pioneer projectiles with an obliquecutting edge;

[0152]FIGS. 4a-c are embodiments of pioneer projectiles with an obliquecutting edge and hollow driven faces;

[0153]FIGS. 5a-c are a plan view, side elevation and end elevationrespectively of a pioneer projectile with an oblique cutting edge;

[0154]FIGS. 6a-c are a plan view, side elevation and end elevationrespectively of a pioneer projectile with a central piercing point andfaceted sides;

[0155]FIGS. 7a-c are a plan view, side elevation and end elevationrespectively of a pioneer projectile with a central cutting edge;

[0156]FIGS. 8a-c are a plan view, side elevation and end elevationrespectively of a pioneer projectile with a central piercing point;

[0157]FIG. 9 is one embodiment of an injectate of the invention shownhoused in a support or device chamber;

[0158]FIG. 10 is another embodiment of an injectate of the inventionshown housed in a support or device chamber;

[0159]FIG. 11 is another embodiment of an injectate of the inventionshown housed in a support or device chamber,

[0160]FIG. 12 is another embodiment of an injectate of the inventionshown housed in a support or device chamber;

[0161]FIG. 13 is another embodiment of an injectate of the inventionshown housed in a support or device chamber;

[0162]FIG. 14 is another embodiment of an injectate of the inventionshown housed in a support or device chamber;

[0163]FIG. 15 is another embodiment of an injectate of the inventionshown housed in a support or device chamber;

[0164]FIG. 16 is cross sectional view of a delivery device of theinvention;

[0165]FIG. 17 is one embodiment of a reusable device according to oneaspect of the invention with one embodiment of a packaged drug accordingto another aspect attached thereto, the device being shown pre-use;

[0166]FIGS. 18a, b, and c illustrate a device substantially similar tothe device illustrated in FIG. 17 in:

[0167] a) its assembled form

[0168] b) at the point where it is fully primed and about to selfactuate; and

[0169] c) in its post actuation position;

[0170]FIG. 19 is a packaged drug according to one aspect of theinvention in which the drug is in a solid or otherwise contained formand follows a pioneer projectile;

[0171]FIG. 20 is a packaged drug according to another aspect of theinvention in which the drug is in a liquid form and is released andinjected via a retractable needle; and

[0172]FIG. 21 is a packaged drug according to yet a further aspect ofthe invention in which the packaging is adapted to hold a drug in asolid or liquid form and in which the end of the packaging is modifiedto be particularly well adapted to skin tensioning.

DETAILED DESCRIPTION

[0173] Referring to the drawings, FIG. 1a is a side elevation of apioneer projectile 10 according to one aspect of the present invention.It is made of a crystalline or amorphous material, preferably a glassymaterial, (e.g. a sugar glass such as trehalose, palatinit,glucopyranosyl sorbitol, glucopyranosyl mannitol, lactitol ormonosaccharide alcohols such as mannitol or inositol) which iswater-soluble and dissolves in the body. The material may include ahardening agent, such as, for example, povidone (pvp). The pioneerprojectile comprises a penetrating face 12 comprising one of morefacets, which has a central point, one or more guiding faces 16 forguiding the pioneer projectile within a central aperture or chamber of aneedleless device for injecting an injectate (comprising the pioneerprojectile and a formulation) thus ensuring the pioneer projectile meetsthe skin at a suitable angle to aid penetration, and a driven face 14.The pioneer projectile has an aspect ratio (width W to height H) ofabout 1.25:1.

[0174] The pioneer projectile cam however take a number of forms andsome further embodiments are illustrated in FIGS. 1b-d, FIGS. 2a-2 c,FIGS. 3a-d, FIGS. 4a-c, FIGS. 5a-c, FIGS. 6a-c; FIGS. 7a-c and FIGS.8a-c.

[0175] Briefly: FIG. 1b illustrates a pioneer projectile with a verysmall aspect ratio of about 1:0.5; FIG. 1c illustrates a pioneerprojectile with an aspect ratio of about 1:2; FIG. 1d illustrates apioneer projectile with a blunt and planar penetrating face 12, and anaspect ratio of about 1:0.2; and FIG. 1e illustrates a pioneerprojectile which does not have a guiding face 16 but consists of apenetrating face 12 and a driven face 14.

[0176]FIGS. 2a to 2 c illustrate variations in the driven face 14. Thusin FIG. 2a the driven face is completely hollowed forming a void 18which can hold, at least in part, at least one therapeutic compound orcompound containing formulation. In FIG. 2b the hollow 18 has a flatbottom 20 and in FIG. 2c it has a concave bottom 22.

[0177] Of course, the penetrating face 12 need not have a central pointand FIGS. 3a-d, and 4 a-c illustrate embodiments in which the pioneerprojectiles have an oblique cutting edge 24.

[0178] The shape of the penetrating face can, as noted above, take anumber of forms as exemplified with reference to FIGS. 5-8. In each ofthese FIGS. a) is a plan view; b) is a side elevation and c) is an endelevation. Thus:

[0179] In FIG. 5 the pioneer projectile is circular in x-section (FIG.5a), has an oblique cutting edge 24 (FIG. 5b), and a planar penetratingface 12 (FIG. 5c).

[0180] In FIG. 6 the pioneer projectile is circular in x-section (FIG.6a), has a central point 26 (FIG. 6b), and four facets 28 making up thepenetrating face 12 (FIG. 6c).

[0181] In FIG. 7 the pioneer projectile is circular in x-section (FIG.7a), has a central cutting edge 30 (FIG. 7b), and two facets 28 makingup the penetrating face 12 (FIG. 7c).

[0182] In FIG. 8 the pioneer projectile is circular in x-section (FIG.8a), has a conical penetrating face (FIG. 8b), culminating in a point 30and a penetrating face 12 (FIG. 5c).

[0183] Of course the pioneer projectile need not be circular in crosssection but could be, for example, three sided (triangular), four sided(square) or indeed any other suitable shape.

[0184] A pioneer projectile might be manufactured in a number of wayssuch as by moulding, extrusion or sectioning a rod of the material.

[0185] Preferably the pioneer projectile will dissolve in the tissue ina matter of minutes or hours depending on the material used.

[0186] The pioneer projectile together with at least one therapeuticcompound or formulation forms an injectate.

[0187] The physical characteristics of the formulation are veryimportant to ensure that the injectate can be administered to the skinin a reliable and repeatable manner

[0188] The formulation could take a number of forms:

[0189] In one embodiment it might take the form of a paste. This can beachieved by mixing the active drug with the appropriate excipients toend up with consistency, say, like toothpaste. The excipients wouldobviously need to maintain the active ingredient in a condition suchthat it was still active during manufacture, storage and administration.

[0190] In other embodiments the formulation will be a semi solid, gel,solid or contained liquid.

[0191] The therapeutic component of the formulation might be present inone or more of the following formats:

[0192] 1. Pure drug;

[0193] 2. With excipients to alter the physical characteristic of thematerial;

[0194] 3. With excipients to bulk out the active ingredient;

[0195] 4. With excipients to buffer the active ingredient;

[0196] 5. With excipients to change the release profile of the activeingredient; and

[0197] 6. As a mixture of more than one therapeutic compound.

[0198] The formulation can be designed to give the desired releaseprofile for the application. This might involve either a sustainedrelease formulation or a quick dissolving formulation for immediaterelease into the body. In some cases, such as for the administration ofinsulin, a formulation might be required that provides an immediaterelease of some of the therapeutic compound and then a sustained releaseof another component in the formulation. This might for example beachieved by having the formulation in a plurality of parts or byincorporating a medicament into the pioneer projectile.

[0199] Alternatively the therapeutic compound might be formulated assmall beads. A number of the beads could be lined up in the devicebehind a pioneer projectile. On actuation of the device the pioneerprojectile pierces the skin and the beads are pushed into the skinbehind the pioneer projectile.

[0200] The therapeutic component of the formulation must of course notreact with the material used for the pioneer projectile or the materialsused in the delivery system.

[0201] FIGS. 9 to 15 are some embodiments illustrating injectates andformulations of the invention.

[0202] In FIG. 9 an injectate 40 comprises a pioneer projectile 10 and aformulation 42. The formulation is in a contained state supported by itsown viscosity or a membrane 44. The formulation is thus a containedliquid or a solid. The injectate may be self-supporting or contained inan optional support 46 which may be a chamber 76 of a device or athrowaway component.

[0203] In FIG. 10 the formulation is a high viscosity liquid, gel, pasteor semi-solid.

[0204]FIG. 11 illustrates an injectate comprising a plurality ofdifferent formulations 42 a, 42 b and 42 c.These could be formulationswith different release profiles or different active ingredients, forexample combination therapies. Though not illustrated there could bemembranes between the components e.g. lipid soluble membranes betweenwater-soluble formulations and or an end piece.

[0205]FIGS. 12, 13 and 14 illustrate injectates with different solidformulations. In FIG. 12 the solid formulation takes the form of beads46. In FIGS. 13 and 14 they are granules, particles or crystals 48.

[0206] In FIG. 15 a barrier 50 is shown between the formulation 42 andthe pioneer projectile 10.

[0207] The skilled man will of course realise that the featuresillustrated with reference to one embodiment could easily be applied toother embodiments.

[0208] An injectate will be introduced into a human or animal using adevice that injects the injectate in a needleless manner.

[0209] One such device is illustrated by way of example only in FIG. 16.

[0210] The needleless injection device 60 is shown in the primedposition. It comprises an outer housing or holder 62 the lowermost end64 of which is slidably mounted over the uppermost end 66 of aninnermost casing 68.

[0211] At the lowermost end 70 of innermost casing 68 is fitted adisposable component 72 such as, for example, a drug cassette. Thedisposable component comprises a casing 74 having a central aperture orchamber 76 in which is mounted the injectate 40 comprising the pioneerprojectile 10 and the formulate 42. A large headed ejector pin 78comprising a flat head 80 and an elongate body 82 is positioned over theinjectate 40 so that when the ejector pin is contacted, in use, by astriker 84 it is pushed along the aperture or chamber 76 and out intothe patient. A resilient member 87, such as a rubber block urges theejector pin back a little after injection.

[0212] The disposable component 72 is loaded into the needlelessinjection device, by for example, screwing it into the lowermost end 70of the inner housing 68. Mounted within the innermost housing 68 is astriker guide 86 having a surface 88 which maintains a detent 90 in theloaded position (shown) and houses an actuating mechanism or spring 92and spring follower 94.

[0213] The disposable component 72 is shaped such that when it is incontact with the skin it pretensions it prior to actuation. This ensuresthat the dosage will penetrate the skin rather than just stretch theskin.

[0214] The injector pin 78 is designed to push the injectate beyond theend of the device by up to (say) 2.5 mm. This means that the end of theinjector pin (which preferably has the same profile and diameter as theend of the pioneer projectile) might just penetrate the skin but itwould ensure that the injectate has been filly administered into theskin.

[0215] Prior to actuation, the tip of the injectate might be in contactwith the skin. However, it is preferred that the tip is a fewmillimetres away from the skin prior to actuation. This ensures that theinjectate is moving when it impacts the skin and also ensures that thetip of the injectate does not start to dissolve, and therefore softenthe tip, with any moisture from the skin surface when the device isplaced on the skin.

[0216] To use the device 60 the outer most casing is retracted (pulledin the direction of arrow A) so that it slides against the innermosthousing 68. This action causes the spring 92 to be compressed, and thedetent to be moved from a vertical position to the position shown whereit is held stable against surface 88. In the process a quill spring 96stabilises the detent by abutting against a surface 98. Once loaded thedisposable component, is screwed into the end 70 of the innermosthousing 68 of the device 60.

[0217] The injector pin 78 that pushes the injectate into the skin ispreferably, (but not necessarily) in contact with the injectate prior toactuation.

[0218] To actuate the device a user, for example, grips the devicearound the outer housing 62 with their thumb over the end cap 102. Theend face 100 of the disposable component 72 is positioned against apatient's skin, which should be held taught, and the outer housing 62 ispushed in a direction away from arrow A. This action causes theoutermost casing to slide over the inner housing 68. As it does so thedetent is caused to rotate about it's axle 104 as a result of the detentriding up inclined wall 106. This forces the quill spring 96 out (asshown by the broken line). When the detent reaches a vertical positionthe coil spring releases its stored energy and assists in ensuring thestriker 84 travels along the striker guide 86 until it contacts the head80 of the ejector pin 78 with a force that causes the injectate 40 topierce the skin. The ejector pin 78 continues to push the formulation 42into the patient to the required depth, which is determined by thelength of the injectate and the extent to which it is pushed by theejector pin 78. The rubber stop 87 is squashed by the ejector pin head80 during delivery of the injectate but the elastic properties of therubber stop 87 enable the tip of the ejector pin to be withdrawn intothe disposable component 72 of the device.

[0219] Injection Sites

[0220] The injectate could potentially be injected in a wide number ofsites across the human or animal body. The easiest direction toadminister the injectate is perpendicular to the skin and so with mostskin sites this would mean penetrating the epidermis into the dermisand, depending on the skin thickness, into the subcutaneous layers ormuscle. The ‘best’ injection sites might therefore be those where thereis the smallest density of nerve endings to avoid any pain that might beassociated with the injection. This might include injections to the backor to the lobe of the ear.

[0221] Alternatively, injection sites might include those with a thickerepidermis so that the injectate does not penetrate into the dermis wherethe nerve endings are located. The injectate might be injected obliquelyinto the skin so that it is located totally in the epidermis. The sameresult might be achieved by injection into a fold of skin that has beenpinched.

[0222] The elastic properties of the skin can be employed to seal theskin after the injectate has been administered, as is often the casewith splinters. This ensures the drug does not leak from the skin as itdissolves.

[0223] The most likely area of the body for drug administration withthis technology is the stomach because of the high fat content and easyaccessibility for self-administration. An alternative might be the thighalthough this is often less accessible if the recipient is wearingtrousers.

[0224] Product Applications

[0225] There are many possible product applications for this technologybecause of the doses that are achievable including therapeutic,prophylactic and diagnostic applications. Illustrative examples include,but are not limited to:

[0226] Conventional Vaccines—first and third world applications orveterinary applications;

[0227] Insulin;

[0228] Migraine Treatments; and

[0229] Hormones.

[0230] The term “at least one therapeutic compound or a formulationcontaining at least one therapeutic compound” as used in thisapplication is intended to cover prophylactic and diagnosticapplications as well as therapeutic applications.

[0231] The maximum dose that could be delivered using the technique willdepend upon a number of factors. However, an injectate with an overalllength of approximately 4.0 mm and a diameter of approximately 1.0 mm(similar to a 19G venflon) would be sufficient to allow a dose ofapproximately 2 mg of a standard therapeutic in one administration. Thismagnitude of dose would be suitable for each of the applicationsexemplified above. If several doses of injectate are deliveredsimultaneously then there is the potential for an even larger number ofapplications.

[0232] Delivery of the injectate will be very quick and any painassociated with the delivery technique should not be any worse than aneedle of similar dimensions. If the delivery technique were painfulthen it would be possible to anaesthetise the tissue prior to theinjection. To avoid needles then this anaesthetic might be given with apatch, a spray or a cream.

[0233] The device illustrated in FIG. 17 is a (reusable) drug deliverydevice (210), with a packaged drug (2100) fitted thereto. It comprisesvery few components. They include

[0234] i) a housing (212);

[0235] ii) a means (214) for generating a force capable of pushing adrug (216) from a packaging (218) into a human or animal body;

[0236] iii) a means (220) for transmitting said force to push the drug(216) from the packaging (218) into the human or animal body;

[0237] iv) a means (222) for receiving a packaged drug (2100);

[0238] v) a means (224) for priming the device; and

[0239] vi) a means (238,242 b) for triggering the device.

[0240] In the embodiment shown the device is primed and triggered in asingle action.

[0241] The delivery device (210) which may be absent of the packageddrug (2100) is spring powered. It can deliver the drug or a formulationcontaining a therapeutic compound (hereafter drug) in a solid,semi-solid or liquid form. By altering the form of the packaged drug(2100) the device can be used to either deliver drugs through aretractable needle (FIG. 20), or behind a “pioneer projectile” (FIGS. 19and 21). It can also be used to deliver a solid drug splinter.

[0242] Looking at the device in more detail it comprises a number ofcomponents which are readily assembled and easily sterilised makingmanufacture cheap.

[0243] The body of the device comprises a three part housing (212)comprising a first housing component (212 a) defining an upper barrel(228) which houses the force generating means (214), a second housingcomponent (212 b) defining a lower barrel (230) which houses thepackaged drug (2100) and the means (220) for transmitting the force topush the drug (216) from its packaging (218). The first and secondhousing components (212 a; 212 b) connect to one another, and a thirdhousing component (212 c), which preferably takes the form of a screwcap (232), fits over the end of the first housing component to close offthe upper barrel (228).

[0244] Within the upper barrel (228) is fitted the means (214) forgenerating the force capable of pushing the drug (216) from itspackaging. In the embodiment shown this takes the form of a mechanicalcoil spring which can generate a force of from about 101-40 N, morepreferably 15-35 N and most preferably 18-31 N. The spring is connectedat its lower end to a spring follower (236) which is slidably mounted inthe upper barrel (228). Above the spring is a compression bar (234)which provides a contact surface against which the spring can act. Byscrewing or unscrewing the cap (232) from the housing component (212 a)the spring can be caused to compress or relax thereby providing a meansfor adjusting the force that can be generated by it. In FIG. 17 thespring is shown at minimum pre-load.

[0245] The upper barrel (228) and lower barrel (230) are separated fromone another by a wall (242) with a communicating aperture (243) thereinand it is on the upper surface (242 a) of this wall that the springfollower (236) sits. The means (220) for transmitting the forcegenerated by the spring takes the form of an impact hammer one end (220a) of which passes through the communicating aperture (243) where itcontacts spring follower (236). In use the uppermost end (220 a) of theimpact hammer slides through the communicating aperture (243) pushingthe spring follower (236) up the upper barrel (228) causing the springto be compressed thus priming the device.

[0246] Within the lower barrel is housed not only the majority of theimpact hammer (220), but a slewing spring (244) and a sliding piston(248) having an aperture (246) therein, such that the lower barrel canoperatively communicate with the packaged drug (2100) which is securedto the device via the receiving means (222) provided at the deviceslowermost end (249).

[0247] The stewing spring functions to draw the longitudinal axis of theimpact hammer off centre (FIG. 18a) in the devices rest position.However, the hammer is adapted by way of a shaped shoulder region (238),(which in a preferred embodiment is substantially frustoconical, asillustrated) to be drawn into axial alignment with the aperture (246) inthe sliding piston, against the action of the stewing spring (244), suchthat when it is filly primed the device automatically actuates.Accordingly the lowermost surface (242 b) of the wall (242) is shaped toreceive the shaped shoulder region (238) of the impact hammer and causethe impact hammer to be axially aligned with the aperture (246) in thesliding piston (248) such that it is driven by the spring (214) throughthe aperture (246) in the sliding piston (248) where it contacts a drivepin (2108) or other element causing the drug (216) to be pushed out ofits packaging (218) into the human or animal. In contrast with the FIG.17 embodiment it should also be noted that the end (220 a) of the impacthammer graduates to a point (being substantially conical) and is seatedin a similarly shaped recess (236 a) in the spring follower (236). Theshaping of the hammer end (220 a) and the provision of the similarlyshaped recess (236 a) in the spring follower (236) farther improvesreliability of actuation.

[0248] By comparison of FIG. 18a with FIGS. 18b and c it will beapparent that once a packaged drug (2100) has been attached to the lowermost end (249) of the device (210) it can be actuated by a user holdingthe device about it's housing (212) and pressing the device (210) firmlyagainst the patients skin. This causes first the skin to be tensionedand then the packaged drug (2100) slides up the lower chamber (230)pushing the piston (248) which in turn pushes the impact hammer (220).As it does so the upper end (220 a) of the impact hammer pushes againstthe spring follower (236) causing the spring (214) to be compresseduntil the necessary drive force is reached. This is at the pointillustrated in FIG. 18b. At this point the shaped shoulder region (238)is drawn into the shaped lowermost surface (242 b) of wall (242), theaction of the stewing spring (244) is countered, the spring (214) isfully charged and the impact hammer (220) axially aligned with theaperture (246) in the sliding piston (248) such that it willautomatically actuate, the spring (214) forcing the impact hammer (220)through the aperture (246) in the piston (248) causing it to push thedrive pin (2108) which in turn, depending on the mechanism employed inthe packaged drug (2100) (see FIGS. 19 to 21) causes the drug to bedispensed into the human or animal. Significantly the longitudinal axisof the impact hammer can't be aligned with the aperture (246) in thesliding piston (248) until it reaches the set actuating force which isset to coincide with the point at which the shaped shoulder region (238)contacts the shaped lowermost surface (242 b) of wall (242) thusproviding a safety mechanism against accidental actuation. When itreaches this point triggering is automatic and the device is actuated(FIG. 18c).

[0249] It should be noted that on actuation the hammer moves only ashort distance, less than 10 mm, more preferably less than 5 mm andtypically about 3 mm before impacting the drive pin and therefore moves(say) approx 5 mm before the pioneer projectile strikes the skin. Thismeans that the maximum force and impact are all in the first fewmillimetres of travel, when the maximum force is required to pierce theskin. Through the rest of the delivery, the force is reducing as themain spring power is diminishing and also the stewing spring is beingcompressed (FIG. 1c). This means that the force tapers off during thesecond half of the delivery when less force is required.

[0250] Therefore the force profile through the whole delivery matchesthe requirements i.e. a high force and impact to pierce the skin andthen a reduced force to push the injectate into the skin

[0251] In the case of a reusable device the packaged drug is removedfrom the device and discarded. The stewing spring will assist in thisaction. As the packaged drug (2100) is removed from the device theslewing spring (244) acts to draw the impact hammer (220) so that it isnot axially aligned with the aperture (246) in the piston (248) and thedevice (210) is ready to receive a new packaged drug.

[0252] Such a device can be used to dispense a drug in a variety ofdifferent forms depending on how it is packaged.

[0253] To demonstrate the versatility of the device three differentdesigns (FIGS. 19, 20, and 21) of packaged drug (2100) are illustratedas suitable for use with the device. All three embodiments illustratethe dispensing of a single dose but the skilled man will appreciate thatmulti-doses could also be dispensed simultaneously or sequentially withthe device of the invention. Similarly, the device could be produced ina pre-primed form with the packaged drug forming an integral part of thedevice.

[0254] Referring to FIG. 19, in one embodiment the packaged drug (2100)takes the form of an end piece which is adapted to be slidably mountablein the device (210). The packaging (218) takes the form of a two-piecehousing (218 a, 21Sb), thereby simplifying construction and assembly. Afirst housing element (218 a) is the shape of a hollow inverted “T” andcomprises a region (2102) (the stem of the “T”) which serves in use toslidably engage the device (210) allowing the packaged drug to slide upthe lower chamber (230) of the device (210), and a “cross piece” againstwhich the second element (218 b) abuts. A central channel (2106 a) runsthrough the middle of the stem exiting at the crosspiece. The secondelement (218 b) comprises an end (2104) which is shaped to tension theskin. The second element (218 b) is also substantially the shape of aninverted T and has a channel (2106 b) running down the centre axis ofthe inverted T. The respective channels (2106 a, 2106 b) communicatewith one another to form a single channel (2106) which runs rightthrough the packaging (218). The channel (2106 b) houses a pioneerprojectile (2110) and the drug (216) or a drug splinter (effectively2110, 216), the skin contacting end of which is set a few millimetres infrom the skin tensioning surface of the device to ensure it is moving atthe requisite speed when it contacts the skin. It also houses the lowerend (2108 b) of the drive pin (2108). At the end remote from the skintensioning surface the channel (2106 b) opens out to house a resilientmember e.g. a spring (2114). The placing of a resilient member under thehead (2108 a) of the drive pin allows the drive pin to be withdrawn backinto the housing immediately after actuation. The drive pin (2108) isslidably mounted in the channel (2106) so that when the head isdepressed by the hammer of the device the drive pin moves down thechannel pushing the pioneer projectile and drug (2110, 2216) from thechannel (106 b) into the human or animal body. The pioneer projectile(2110) and drug (216) are held in place in the channel (2106 b) by, forexample, a breakable membrane (not shown) or appropriate frictionalmeans e.g. one or more markings or splines on either the pioneerprojectile, drug and or channel (2106 b) surface.

[0255] The packaged drug illustrated in FIG. 19 is suitable for theinjection of a “contained” drug behind a pioneer projectile which canpenetrate the skin and create a channel into which the drug is pushed asdescribed. This type of packaged drug is also suitable for theadministration of drug splinters or rods of a solid therapeutic compoundwhich have a sharp tip as per WO 94/22423. The therapeutic compound ortherapeutic compound and tip are initially located in the channel (2106)of the packaging (218). The distal end (2108 b) of the drive pin may ormay not be in contact with the uppermost end of the therapeutic compoundprior to actuation. When the drive pin head (2108 a) is struck by theimpact hammer the drive pin (2108) pushes the therapeutic compound (andpioneer projectile, if included) into the target tissue.

[0256] The end of the drive pin may just penetrate the outer layers ofthe skin to ensure that the therapeutic compound is completely deliveredinto the skin. Alternatively, the packaged drug may include a short rod(or rods) of a placebo or pharmaceutical compound between the end of thedrive pin and the therapeutic compound, which can be used to push thetherapeutic compound fully into the skin. In this case it would notmatter if the placebo rods entered the skin but it would ensure that thedrive pin did not have to penetrate the skin. The benefits of this arethat the drive pin would not be left protruding from the packaged drugfollowing the administration and would not be contaminated with bodilyfluids and it would therefore not pose a health risk in terms ofdisposal. An alternative is to include a piece of rubber or foam, or asillustrated a light spring (2114), under the head (2108 a) of the drivepin to ensure that the tip of the drive pin is withdrawn into the spentpackaging after administration.

[0257]FIG. 20 illustrates an alternative design of a packaged drug foruse with a device according to the invention. The packaged drugcomprises a two piece housing (218 a, 218 b) which is identical to thatof the FIG. 19 embodiment. This simplifies manufacture as the housingcomponents can be used for a packaged drug which is solid (as per theFIG. 19 embodiment) or one which is liquid. In order to be adapted todispense a liquid a needle (2112) sits in the channel (2106), it's lowerend (2112 b) being in the channel (2106 b) of housing component (218 b)and its upper end (2112 a) extending into the channel (2106 a) ofhousing component (218 b). The needle (2112) is obliquely cut at bothends to provide sharp points. Attached to the upper end (2112 a) of theneedle is a support plate (2113) on which is seated a resilient orcompressible spacer (2126) which extends above the tip of the upper end(2112 a) of the needle. Seated on the spacer (2126) immediately abovethe tip of the needle (2112) is a liquid drug containing receptacle(2120). The receptacle comprises one or more side walls (2121) and apuncturable base (2122) which together define a receptacle cavity whichis filled with the drug (216) through an opening (2124). The receptacleis sealed by a drive pin or element (2108) which sits in the receptacleopening (2124).

[0258] In use the hammer of the drug delivery device contacts the driveelement head (2108 a) causing the receptacle to be pushed down thechannel (2106 a) of the housing element (218 a). The spacer (2126) iscompressed causing the needle to puncture the base (2122). Consequentlythe needle (2112) is filled by some of the drug contents (216) of thereceptacle thereby expelling air from the needle prior to piercing ofthe skin and delivery of the drug. The force exerted on the supportplate (2113) forces the needle into the skin where the liquid drugcontents (216) drain into the human or animal through the tract formedby the needle (2112). As the user of the device removes the device fromthe skin, the drug package is pushed substantially out of the end of thedevice by the action of the stewing spring, and the needle is withdrawninto the drug package by the action of the spring (2114).

[0259] In yet a further embodiment, and as illustrated in FIG. 21 thereis a packaged drug (2100) which is adapted to hold a drug (216) in anystate, liquid, semi solid or solid. As in the previous embodiments thehousing (218) preferably takes the form of a two piece housing (218 a,218 b) although in this case the housing elements are shapeddifferently. In channel (2106 b) of the second housing element (218 b)is housed a pioneer projectile (2110) and the lowermost part of a drugcontaining receptacle (2120) in the form of a thin walled metal tubewhich is scaled with a breakable membrane (2122). The tube terminates atit's uppermost end in a lip (2121) on which rest a pair of flexible arms(2128) of a drive element (2108). The receptacle is sealed by the driveelement (2108). At the end remote from the skin tensioning surface ofthe second housing element (218 b) is a ramped surface (2130). Theuppermost part of the drug containing receptacle (2120) and the driveelement (2108) sit in a cavity between the housing elements (218 a, 218b) and which can be considered an extension of channel (2106 a) formedin the first housing element (218 a). The end (2104) in this embodimentis particularly well suited to skin tensioning and includes an annularring (2105) located immediately about the channel (2106) exit Theannular ring in this embodiment is about 3 mm in diameter (including thechannel which is about 1 mm in diameter) and depth. By way of comparisonthe end (2104) has a diameter of about 16 mm. The depth and width neednot be 3 mm by 3 mm but should generally be in the range 1.5 mm to 6 mm.Any more than this and it may cause pain and bruising and any less thanthis and it may not adequately tension the skin. This annular ring whichmay be a whole ring or a broken ring comprising a number of projectingelements disposed in a substantially annular fashion about the channelexit could be a feature of any embodiment. To simplify construction inthis embodiment the drive pin head (2108 a) is produced as separatecomponent to the lower and elongate end (2108 b) of the drive pin.

[0260] In use the hammer of the drug delivery device contacts the driveelement head (2108 a) causing the receptacle to be pushed down thechannel (2106 b) as a consequence of the force exerted by the flexiblearms (2128) of the drive element (2108) against the lip (2121) of thereceptacle (2120). This causes the pioneer projectile (2110) to bepushed into the patient. Once the pioneer projectile has entered thepatient the flexible arms (2128) of the drive element (2108) contact theramp surface (2130) of the second housing element (218 b) and are causedto flex apart and ride over the lip (2121) and/or snap. As a consequencethe lower part (2108 b) of the drive element is able to move down thereceptacle (2120) pushing the drug (216) contents out into a tractformed by the pioneer projectile (2110). Preferably the end of thereceptacle which takes the form of a thin walled tube just enters theskin before the drug is delivered. This ensures that if a liquid drug isused the drug follows the pioneer projectile into the skin rather thanescaping along the skin surface.

[0261] The main advantage of the FIG. 21 embodiment is for the injectionof liquids as it ensures that the liquid is contained during theadministration and is guided by the thin walled metal tube into thetarget tissue. However, the drug contents need not be restricted toliquids.

[0262] A feature of the device illustrated which further distinguishesit from other hand powered systems is that the force generated by thespring is the delivery force and there is substantially no additionalforce generated by the operator due to the gradual priming andinstantaneous actuation when the device reaches the delivery force set.

[0263] In contrast devices which include a break tab or other snap meansto actuate the device can't have the force carefully controlled and as aconsequence the greater the force exerted by the user the greater thevelocity of impact by the drug with the skin.

[0264] With the system detailed in this application the hand forcecompresses the main spring to a preset point at which the drug packageis inserted to virtually its maximum point within the device. At thispoint the actuation takes place and the predetermined spring strengthdelivers the drug. Any extra force by the hand is dissipated over thewhole of the area of the end of the device.

[0265] An alternative way of viewing this is to consider the skin as asponge. In devices utilising snap tabs, when the snap tabs are brokenall the force by the hand is pushing the drug and the resilience of theskin will start to push the bottom half of the device (part not held inhand) back towards the hand. This may result in a less good seal withthe skin and, in theory, if the hand force stops immediately the snaptabs are broken then the drug would never be pushed from the device—theyrely on the inertia in the hand to make the injection. In practice thismeans that the user pushes and pushes and then suddenly the tabs breakand the device is pushed into the target possibly causing pain andbruising with the device. In the present injection the skin iscompressed by a steady hand force. At the point of actuation the mainspring controls the delivery of the drug and the hand maintains (butdoes not suddenly increase) the force on the skin to ensure a goodcontact with the skin. If at any point before actuation the sensation onthe skin is painful then the injection site can be altered or theinjection aborted rather than causing further pain and/or bruising.

[0266] Devices of the type described have been demonstrated by theapplicant to be capable of delivering a drug as demonstrated by thefollowing examples:

EXAMPLES

[0267] Initial experiments were carried out with non pharmaceuticalmaterials to demonstrate the delivery concept. These experimentscomprised the following:

Example 1 Drug Splinters

[0268] A rod of 0.9 mm diameter pencil lead was broken to lengths ofapproximately 6 mm and a point was sanded on one end of each length anda flat on the other to create solid splinters. The splinters were placedin the drug package shown in FIG. 19 and successfully administered topig skin using a prototype delivery system.

Example 2 Pioneer Projectile Followed by a Solid Rod

[0269] The same pencil lead detailed in example 1 above was cut intoshort lengths of approximately 3 mm in length. These had a point sandedon one end and a flat on the other end to create pioneer projectiles.Further rods of the same pencil lead were cut at approximately 4 mm inlength and had both ends sanded flat. When a pioneer projectile and asolid rod were placed in a drug package as shown in FIG. 19 they weresuccessfully administered to pig skin using a prototype delivery system.

Example 3 Pioneer Projectile Followed by a Soft Rod

[0270] A soft rod of wax was extruded through a die and rods ofapproximately 4 mm in length were cut with a flat at each end. Furthersections were cut with a point at one end and a flat at the other end.When a pointed section (identical in shape and size to the splinter usedin example 1) was administered to pig skin using a drug package as shownin FIG. 19 the wax did not pierce the skin but was flattened on the skinsurface. When a rod of the same waxy material was placed behind apioneer projectile used in example 2 and administered to pig skin usinga drug package as shown in FIG. 19 then both the pioneer projectile andthe waxy material were successfully delivered into the tissue. The waxmaterial used for this experiment could easily be squashed between afinger and a thumb.

Example 4 Pioneer Projectile Followed by Solid Beads

[0271] Beads of diameters 0.5-0.75 mm were placed in a drug package, asshown in FIG. 19, behind a pioneer projectile as detailed in example 2.The pioneer projectile and all the beads were successfully administeredto pig skin using a prototype delivery system.

[0272] The experiments outlined above demonstrated that a range ofdifferent materials could be delivered behind a solid pioneerprojectile. Ideally it is preferred that the pioneer projectile ismanufactured from pharmaceutical grade compounds that will dissolve inthe target tissue. Two processes have been used to produce such pioneerprojectiles as outlined below:

Example 5

[0273] A hot melt of sugars is produced which can then be moulded intothe correct form for a pioneer projectile or extruded to produce longrod. If an extrusion process is used then the pioneer projectiles can becut to shape from the soft extrudate or the sharp ends of the pioneerprojectile can be formed when the extrudate has solidified. This processproduces a material similar to a boiled sweet which can be very hard andincorporate a sharp point on one end.

Example 6

[0274] A mix of powders is produced using pharmaceutical grade sugarstogether with a hardening agent such as polyvinylpyrolidone (PVP). Thepowder blend is extruded through a die to produce a long rod of thecompound. Some blends require a lubricant to facilitate the extrusionand binding process such as water or ethanol. The pioneer projectilesare formed by cutting the long rod into short sections. This process canbe facilitated by using a hot knife. If necessary, the point or flat endof the pioneer projectile can be created by sanding or filing a shortrod of the extrudate.

1. A method of delivering at least one therapeutic compound or aformulation containing at least one therapeutic compound to a human oranimal in the form of a needleless injection comprising: i) Penetratingthe skin with a water soluble, lipid soluble or otherwise biodegradablepioneer projectile having a diameter of less than 3 mm which is left inthe human or animal; and ii) Introducing directly, or substantiallydirectly, behind the pioneer projectile, the at least one therapeuticcompound or the formulation containing the at least one therapeuticcompound, which at least one therapeutic compound or the formulationcontaining the at least one therapeutic compound is provided anddelivered in a contained state.
 2. A method as claimed in claim 1wherein the pioneer projectile is water soluble.
 3. A method as claimedin claim 1 wherein the pioneer projectile is independent of the at leastone therapeutic compound or the formulation containing the at least onetherapeutic compound.
 4. A method as claimed in claim 1 wherein thepioneer projectile is independent of yet forms an integral part of theat least one therapeutic compound or the formulation containing the atleast one therapeutic compound.
 5. A method as claimed in claim 4wherein the pioneer projectile forms a head to the at least onetherapeutic compound or the formulation containing the at least onetherapeutic compound.
 6. A method as claimed in claim 1 wherein the atleast one therapeutic compound or the formulation containing the atleast one therapeutic compound is provided in a liquid form which iscontained in a water soluble, lipid soluble or otherwise biodegradablemembrane.
 7. A method as claimed in claim 1 wherein the at least onetherapeutic compound or the formulation containing the at least onetherapeutic compound is provided in a solid form.
 8. A method as claimedin claim 1 wherein the at least one therapeutic compound or theformulation containing the at least one therapeutic compound is providedas a semi solid or a gel or a paste.
 9. A method as claimed in claim 7wherein the solid form comprises crystals, particles, granules, beads,rods, discs or a combination thereof.
 10. A method as claimed in claim 1in which the skin is penetrated and the at least one therapeuticcompound or the formulation containing the at least one therapeuticcompound is administered at a low velocity.
 11. A method as claimed inclaim 10 wherein the velocity is less than 100 m/s.
 12. A method asclaimed in claim 10 wherein the velocity is less than 10 m/s.
 13. Amethod of facilitating the delivery of at least one therapeutic compoundor a formulation containing the at least one therapeutic compound to ahuman or animal as a needleless injection comprising: i) Providing awater soluble, lipid soluble or otherwise biodegradable pioneerprojectile having a diameter of less than 3 mm capable of penetratingthe human or animal's skin; and ii) Providing directly, or substantiallydirectly, behind the pioneer projectile, the at least one therapeuticcompound or the formulation containing the at least one therapeuticcompound in a contained state.
 14. A water soluble, lipid soluble orotherwise biodegradable pioneer projectile, having a diameter of lessthan 3 mm and which is capable of penetrating the skin of a human oranimal to thereby facilitate the injection of at least one followingtherapeutic compound or therapeutic compound containing formulation in acontained state, comprises: i) A first ‘penetrating’ face which in usepenetrates the human or animal's skin; and ii) Remote from the firstface a second ‘driven’ face which in the course of injection is the faceupon which a driving force is exerted through the contained therapeuticcompound or therapeutic compound containing formulation; characterisedin that said pioneer projectile has an aspect ratio (width to height) ofless than 1:10.
 15. A pioneer projectile as claimed in claim 14 whereinthe pioneer projectile is water soluble.
 16. A pioneer projectile asclaimed in claim 14 which has an aspect ratio of less than 1:8,preferably less than 1:6, more preferably less than 1:4 more preferablystill less than 1:3 and most preferably about 1:1.5.
 17. A pioneerprojectile as claimed in claim 14 that has an aspect ratio of about1:1.5.
 18. A pioneer projectile as claimed in claim 14 that is less than3 mm in width, more preferably less than 2 mm in width and mostpreferably about or less than 1 mm in width.
 19. A pioneer projectile asclaimed in claim 14 that is about 1 mm in width.
 20. A pioneerprojectile as claimed in claim 14 that is less than 10 mm in height. 21.A pioneer projectile as claimed in claim 14 that is from about 1.5 to 2mm in height.
 22. A pioneer projectile as claimed in claim 14 that isfee of any therapeutic compound.
 23. A pioneer projectile as claimed inclaim 14 comprising at least one therapeutic compound.
 24. A pioneerprojectile as claimed in claim 14 in which the skin penetrating facecomprises a cutting element.
 25. A pioneer projectile as claimed inclaim 24 wherein the cutting element comprises a sharp point.
 26. Apioneer projectile as claimed in claim 24 wherein the cutting elementcomprises an oblique edge.
 27. A pioneer projectile as claimed in claim14 wherein the skin penetrating face is blunt or gentle curved.
 28. Apioneer projectile as claimed in claim 14 in which the face forcontacting the therapeutic compound or therapeutic compound containingformulation in a contained state is flat.
 29. A pioneer projectile asclaimed in claim 14 in which the face for contacting the therapeuticcompound or therapeutic compound containing formulation in a containedstate is concave or otherwise hollowed.
 30. A pioneer projectile asclaimed in claim 14 that comprises a glassy material.
 31. A pioneerprojectile as claimed in any of claim 14 that comprises a barriermaterial over at least the face for contacting the therapeutic compoundin a contained state.
 32. A therapeutic compound or therapeutic compoundcontaining formulation which is held in a contained state and adaptedfor introduction into a human or animal in the form of a needlelessinjection behind a water soluble, lipid soluble or otherwisebiodegradable pioneer projectile having a diameter of less than 3 mm.33. A therapeutic compound or therapeutic compound containingformulation as claimed in claim 32 comprising less than 50 mg of atleast one therapeutic compound in a volume of less than 50 mm³, morepreferably less than 10 mg of therapeutic compound in a volume of lessthan 10 mm³.
 34. A therapeutic compound or therapeutic compoundcontaining formulation as claimed in claim 32 which is provided as aliquid contained in a water soluble, lipid soluble or otherwisebiodegradable membrane.
 35. A therapeutic compound or therapeuticcompound containing formulation as claimed in claim 32 which is providedas a liquid with a viscosity of at least 10,000 centipoises morepreferably at least 100,000 centipoises.
 36. A therapeutic compound ortherapeutic compound containing formulation as claimed in claim 32,which is provided in a solid form.
 37. A therapeutic compound ortherapeutic compound containing formulation as claimed in claim 32 whichis provided as a semi solid or a gel or a paste.
 38. A therapeuticcompound or therapeutic compound containing formulation as claimed inclaim 36 which solid form comprises crystals, particles, granules beads,rods, discs or a combination thereof.
 39. A therapeutic compound ortherapeutic compound containing formulation as claimed in claim 32 whichcomprises an end piece beyond the therapeutic compound or therapeuticcompound containing formulation.
 40. A therapeutic compound ortherapeutic compound containing formulation as claimed in claim 32,which comprises a plurality of differently, formulated elements.
 41. Atherapeutic compound or therapeutic compound containing formulation asclaimed in claim 32, which is contained in a cap, cartridge, carousel orcassette.
 42. A therapeutic compound or therapeutic compound containingformulation as claimed in claim 32 that comprises a barrier materialover at least the face for contacting the pioneer projectile.
 43. Aneedleless injectate for injection comprising: a) A water soluble, lipidsoluble or otherwise biodegradable pioneer projectile having a diameterof less than 3 mm; and b) A therapeutic compound or therapeutic compoundcontaining formulation which is held in a contained state behind thepioneer projectile.
 44. A needleless injectate as claimed in claim 43wherein the pioneer projectile and therapeutic compound or therapeuticcompound containing formulation is water soluble, lipid soluble orotherwise biodegradable to differing degrees.
 45. A needleless injectateas claimed in claim 43 wherein the therapeutic compound or therapeuticcompound containing formulation is provided as a liquid contained in awater soluble, lipid soluble or otherwise biodegradable membrane.
 46. Aneedleless injectate as claimed in claim 43 wherein the therapeuticcompound or therapeutic compound containing formulation is provided in asolid form.
 47. A needleless injectate as claimed in claim 43 whereinthe therapeutic compound or therapeutic compound containing formulationis provided as a semi solid or a gel or a paste.
 48. A needlelessinjectate as claimed in claim 43 wherein the therapeutic compound ortherapeutic compound containing formulation is a liquid with a viscosityof at least 10,000 centipoises more preferably at least 100,000centipoises.
 49. A needleless injectate as claimed in claim 46 whereinthe solid form comprises crystals, particles, granules, beads, rods,discs or a combination thereof.
 50. A needleless injectate as claimed inclaim 43 further comprising a barrier between the pioneer projectile andthe therapeutic compound or therapeutic compound containing formulation.51. A needleless injectate as claimed in claim 43 further comprising anend piece beyond the therapeutic compound or therapeutic compoundcontaining formulation.
 52. A needleless injectate as claimed in claim43 wherein the therapeutic compound or therapeutic compound containingformulation comprises a plurality of differently formulated elements.53. A needleless injectate as claimed in claim 43 wherein the injectateis contained in a cap, cartridge, carousel or cassette.
 54. A needlelessinjectate as claimed in claim 43 wherein the pioneer projectile and thetherapeutic compound or therapeutic compound containing formulation arecontained in separate caps, cartridges, carousels or cassettes.
 55. Aneedleless injectate as claimed in claim 43 comprising a barriermaterial separating the therapeutic compound from the pioneerprojectile.
 56. A needleless device (60) for injecting a water soluble,lipid soluble or otherwise biodegradable pioneer projectile (10) havinga diameter of less than 3 mm and at least one contained therapeuticcompound or therapeutic compound containing formulation (42) into ahuman or animal body, said device comprises a housing (62) containing amechanism (92) capable of generating a force which will cause a striker(84) to travel along a striker guide (86), said housing having an endface (100) which is in operative communication with a component (72)comprising a casing (74) having an aperture (76) in which is mounted anejector pin (78) and, therebelow, an injectate (40) comprising a pioneerprojectile (10) and a formulation (42) such that in use the striker willcontact the ejector pin and the injectate will be pushed out of thecasing as a single unit into the human or animal body.
 57. A device asclaimed in claim 56 wherein the means for pushing the pioneerprojectile, through the therapeutic compound or therapeutic compoundcontaining formulation, out of the at least one chamber and into thehuman or animal is a pin, piston, rod or like member.
 58. A device asclaimed in claim 56, which further comprising a power source forinitiating or assisting the pushing.
 59. A device as claimed in claim 58wherein the power source is a mechanical spring.
 60. A device as claimedin claim 58 wherein the power source is a gas spring.
 61. A device asclaimed in claim 56 wherein the power source is a mechanical springwhich is precharged.
 62. A device as claimed in claim 56 wherein thepower source can be recharged.
 63. A device as claimed in claim 56wherein the device is driven manually.
 64. A device as claimed in claim56 which comprises a reusable component and a throwaway component.
 65. Adevice as claimed in claim 64 wherein the component containing thepioneer projectile or the pioneer projectile and the therapeuticcompound or therapeutic compound containing formulation is the throwaway component.
 66. A device as claimed in claim 64 wherein the reusablecomponent and the throwaway component comprise means by which they areconnected to one another.
 67. A device as claimed in claim 56 which isadapted to inject multiple injectates either sequentially orsimultaneously.
 68. A device as claimed in claim 56, which comprises acartridge, carousel or cassette containing a plurality of pioneerprojectiles or a plurality of injectates comprising a pioneer projectileand a therapeutic compound or therapeutic compound containingformulation.
 69. A device as claimed in claim 56, which comprises a capcontaining a single pioneer projectile and a single unit dose of thetherapeutic compound or therapeutic compound containing formulation. 70.A drug delivery device (210) comprising: i) a housing (212); ii) a means(214) for generating a force capable of pushing a drug (216) from apackaging (218) into a human or animal body; iii) a means (220) fortransmitting said force to push the drug (216) from the packaging (218)into the human or animal body; and iv) a means (238, 242 b) fortriggering the device.
 71. A drug delivery device as claimed in claim 70wherein the housing defines: i) an upper barrel (228), at one end of thedevice, which houses the force generating means (214); and ii) a lowerbarrel (230), at the end remote from the upper barrel, which houses: a)a packaged drug (2100); and b) the means (220) for transmitting saidforce to push the drug (216) from the packaging (218) said lower barrelbeing in operative communication with said upper barrel and saidpackaged drug (2100).
 72. A drug delivery device (210) as claimed inclaim 70 further comprising v) a means (222) for receiving the packageddrug (2100); and vi) a means (224) for priming the device.
 73. A drugdelivery device as claimed in claim 70 wherein the means (214) forgenerating a force capable of pushing a drug (216) from a packaging(218) into a human or animal body delivers a force of from 10-40N.
 74. Adrug delivery device as claimed in any claim 70 wherein the means (220)for transmitting said force to push the drug (216) from the packaging(218) causes the drug to be pushed from the packaging at less than 10m/s.
 75. A drug delivery device as claimed in claim 71 wherein saidpackaged drug (2100) is slidably disposed in the means (222) forreceiving the packaged drug.
 76. A drug delivery device as claimed inclaim 71 wherein the packaged drug (2100) is slidably disposed in thelower barrel (230) and comprises a packaging (218) containing a drug(216), said packaging comprising a housing (218 a, 218 b) having achannel (2106; 2106 a, 2106 b) running there through in which isdisposed a drive pin or other element (2108), a skin piercing means(2110; 2112) and the drug (216); said housing further comprising i) aregion (2102) allowing the packaged drug to be slidably mounted to thedrug delivery device (210) at receiving means (222); and ii) an end(2104) adapted to engage and tension the skin.
 77. A drug deliverydevice as claimed in claim 70 wherein the skin piercing means is apioneer projectile (2110), a syringe needle (2112) or the head of a drugsplinter.
 78. A drug delivery device as claimed in claim 70 wherein thedrive pin or other element (2108) has a flat or enlarged head (2108 a).79. A drug delivery device as claimed in claim 70 further comprising aresilient means (2114) below or otherwise in association with the drivepin or other element (2108) to ensure the drive pin is withdrawn afteruse.
 80. A drug delivery device as claimed in claim 70 wherein the means(214) for generating the force capable of pushing the drug (216) is aspring.
 81. A drug delivery device as claimed in claim 80 wherein thespring is a coil or gas spring.
 82. A drug delivery device as claimed inclaim 80 wherein the force generated by the spring is adjustable.
 83. Adrug delivery device as claimed in claim 70 wherein a screw cap (232)and compression bar (234) provide a means for adjusting the forcegenerated by the spring.
 84. A drug delivery device as claimed in claim70 further comprising a spring follower (236).
 85. A drug deliverydevice as claimed in claim 70 wherein the means (220) for transmittingthe force is a striker.
 86. A drug delivery device as claimed in claim85 wherein the striker is a hammer.
 87. A drug delivery device asclaimed in claim 70 wherein a region (238) of the striker is shaped tofit a correspondingly shaped surface (242 b) in a wall (242) separatingthe upper (228) and lower (230) barrels defined by the housing (212)such that the striker (220) is aligned to strike the drive pin (2108) orother element in the packaged drug (2100) on actuation.
 88. A drugdelivery device as claimed in claim 85 wherein the striker comprises asubstantially frustoconical shoulder region (238) which engages asubstantially frustoconical surface (242 b) in the wall (242) separatingthe upper (228) and lower (230) barrels defined by the housing (212).89. A drug delivery device as claimed in claim 70 wherein the means(220) for transmitting the force comprises a substantially conical end(220 a) and the spring follower (236) has a correspondingly shapedrecess (236 a) in the underside thereof.
 90. A drug delivery device asclaimed in claim 70 wherein the packaged drug (2100) and striker (220)are slidably mounted in the device such that the device can be can beprimed by pushing the device against the skin.
 91. A drug deliverydevice as claimed in claim 71 wherein the device comprises a stewingspring (244), a sliding piston (248) having an aperture (246) thereinand the striker (220), all housed in the lower barrel (230) and thedevice is triggered by the sliding of the piston (248) up the lowerbarrel (230) until shoulder region (238) of the striker (220) engagesshaped surface (242 b) and aligns the striker with the aperture (246) inthe sliding piston (248) such that the striker moves down the apertureunder the action of the force generating means (214).
 92. A drugdelivery device as claimed in claim 71 wherein the device is primed andactuated by a single action.
 93. A device as claimed in claim 92 whereinpushing the packaged drug (2100) up the lower barrel (230) withsufficient force causes the device to be primed and actuated.
 94. Adevice as claimed in claim 92 wherein the action of pushing the packageddrug up the lower barrel (230) with sufficient force causes the slidingpiston (248) to move up the lower barrel (230) thereby causing thestriker (220) to be pushed up the lower barrel (230) out of a firstposition in which it is not axially aligned with the aperture (246) inthe sliding piston which operatively communicates with the packaged drugand at the same time acts on a spring follower (236) in the upper barrel(228) causing the spring (214) to be compressed and the device primedsuch that when the required delivery force is generated the striker(220) is axially aligned with the aperture (246) of the sliding piston(248) and is thus actuated such that the spring (214) acts through thespring follower (236) and striker (220) upon the drive pin (2108) or alike element in the packaged drug (2100) to deliver the drug (216) intothe human or animal body.
 95. A device as claimed in claim 70 whereinthe device is primed and acted by two separate actions.
 96. A drugdelivery device as claimed in claim 71 wherein the upper barrel andlower barrel are formed as separate components.
 97. A drug deliverydevice as claimed in claim 70 wherein the drug is in a contained form.98. A drug delivery device as claimed in claim 97 wherein the drug iseither: a liquid contained by a membrane; a liquid with a viscosity ofat least 500 centipoises, more preferably at least 5000 centipoises, andmore preferably still at least 100,000 centipoises; a semi solid, apaste, a gel or a solid.
 99. A drug delivery device as claimed in claim70 further comprising a packaged drug as an integral part of the device.100. A drug delivery device as claimed in claim 70 in which the deviceand/or packaged drug is sealed in a foil pouch or the like to preventingress of for example, moisture, oxygen, light, bacteria or other drugdegrading or contaminating agents.
 101. A drug delivery device asclaimed in claim 70 wherein the tip of the pioneer projectile or needleis positioned a few mm in from end (2104) of the packaging (218) suchthat it is moving when contacting the skin.
 102. A drug delivery deviceas claimed in claim 70 wherein the end (2104) about the exit of thechannel (2106) is in the form of a substantially annular ring locatedimmediately about the channel (2106) exit and having a depth and widthin the range 1.5 mm to 6 mm.
 103. A drug delivery device as claimed inclaim 70 further comprising a positive lock retention system to ensurethe packaged drug (2100) does not come away from the device undergravity yet is free to slide up the device.
 104. A single use drugdelivery device (210) comprising: i) a housing (212); ii) a pre-primedmeans (214) for generating a force capable of pushing a drug (216) froma packaging (218) into a human or animal body; iii) a means (220) fortransmitting said force to push the drug (216) from the packaging (218)into the human or animal body; iv) a packaged drug (2100) forming anintegral part of the device; and v) a means for triggering the device.105. A device as claimed in claim 104 wherein the means for triggeringthe device is an actuation button or like element.
 106. A single usedrug delivery device (210) comprising: i) a housing (212); ii) a means(214) for generating a force capable of pushing a drug (216) from apackaging (218) into a human or animal body; iii) a means (220) fortransmitting said force to push the drug (216) from the packaging (18)into the human or animal body; iv) a packaged drug (2100) forming anintegral part of the device; v) a means for priming (224) the device;and vi) a means (238, 242 b) for triggering the device.
 107. A packageddrug (2100), for use with a drug delivery device, comprising a packaging(218) containing a drug (216), said packaging (218) comprising a housing(218 a, 218 b) having a channel (2106) running there through and inwhich is disposed a drive pin or other element (2108), a skin piercingmeans (2110; 2112), and the drug (216), said housing (218 a, 218 b)further comprising i) a region (2102) allowing the packaged drug (2100)to be slidably mounted to the drug delivery device (210); and ii) an end(2104) adapted to engage and tension the skin.
 108. A packaged drug asclaimed in claim 107 wherein the skin piercing means is a pioneerprojectile (2110), syringe needle (2112) or the head of a drug splinter.109. A packaged drug as claimed in claim 107 wherein the drug is in theform of a drug splinter.
 110. A packaged drug as claimed in any ofclaims 107 wherein the housing is adapted to ensure the packaged drugpositively locks to the device yet is free to slide therein.
 111. Apackaged drug (2100) as claimed in claim 107 wherein the packaging (218)is substantially T-shaped.
 112. A packaged drug as claimed in claim 107wherein the drive pin has a flat and/or an enlarged head (2108 a). 113.A packaged drug as claimed in claim 107 further comprising a resilientmeans (2114) below the drive pin head to ensure the drive pin iswithdrawn after use.
 114. A packaged drug as claimed in claim 107 inwhich the packaging comprises a two-part housing (218 a, 218 b).
 115. Apackaged drug as claimed in claim 107 comprising a pioneer projectile.116. A packaged drug as claimed in claim 107 wherein the drug is held ina contained state.
 117. A packaged drug as claimed in claim 107 whereina hollow injection needle (2112) is disposed in the channel (2106)towards end (2104) and a contained liquid drug (216) is disposed in thechannel (2106) there above.
 118. A packaged drug as claimed in claim 117wherein the contained liquid drug comprises a receptacle (2120) slidablydisposed in the channel and having a puncturable base (2122), a top(2124) sealable with the drive pin or element (2108) for pushing i) thereceptacle against the needle, and ii) the needle into the human oranimal body thereby causing the release of the drug (216) out of thechannel and into the human or animal body when it is acted upon by thedevice (210)
 119. A packaged drug as claimed in claim 117 furthercomprising a resilient spacer (2126) between the needle and thereceptacle.
 120. A packaged drug as claimed in claim 117 furthercomprising a resilient means (2114) associated with the needle such thatthe needle is automatically withdrawn after use.
 121. A packaged drug asclaimed in claim 117 in which the needle is sharp at both of its ends.122. A packaged drug as claimed in claim 107 comprising a receptacle(2120) housing the drug (216) said receptacle having a breakable base(2122) and being sealed by the drive pin (2108) or other element whichdrive pin or other element comprises an elongate body (2127) and aplurality of flexible arms (2128).
 123. A packaged drug as claimed inclaim 122 in which the arms (2128) of said element (2108), in use, rideover one or more ramped surfaces (2130) provided on the housing suchthat they are displaced and/or break away from the elongate body (2127)so the elongate body of the drive pin can travel down the receptacle(2120), causing the drug (216) to be expelled from the base (2122) ofthe receptacle which breaks under the pressure exerted thereon.
 124. Apackaged drug as claimed in claim 122 further comprising a pioneerprojectile (110) below the base of the receptacle.
 125. A packaged drugas claimed in claim 107 wherein a placebo is disposed behind the drug(216).
 126. A method of delivering a drug to a human or animal bodythrough the skin comprising administering a drug using a device asclaimed in claim 70 or a packaged drug as claimed in claim 107.